同型半胱氨酸与卒中:来自孟德尔随机法则的证据  

Homocysteine and stroke: Evidence on a causal link from mendelian randomisation

作　　者：Casas J.P. Bautista L.E. Smeeth L. P. Sharma 黄卫东 

机构地区：[1]Hammersmith Hospitals Acute S., Imperial College London, London, United Kingdom Dr.

出　　处：《世界核心医学期刊文摘（神经病学分册）》2005年第6期7-8,共2页Digest of the World Core Medical Journals:Clinical Neurology

摘　　要：Background Individuals homozygous for the T allele of the MTHFR C677T polymorphism have higher plasma homocysteine concentrations (the phenotype) than those with the CC genotype, which, if pathogenetic, should put them at increased risk of stroke. Since this polymorphism is distributed randomly during gamete formation, its association with stroke should not be biased or confounded. We investigated consistency between the expected odds ratio for stroke among TT homozygotes, extrapolated from genotype - phenotype and phenotype- disease studies, and the observed odds ratio from a meta- analysis of genotype- disease association studies. Methods We searched MEDLINE and EMBASE up to June, 2003, for all relevant studies on the association between homocysteine concentration and the MTHFR polymorphism, and until December, 2003, for those on the association between the polymorphism and the risk of stroke. Pooled odds ratios and 95% CI were calculated by random- effects and fixed- effects models. Consistency between expected and observed odds ratios was assessed by interaction test. Findings 111 studies met the selection criteria. Among 15 635 people without cardiovascular disease, the weighted mean difference in homocysteine concentration between TT and CC homozygotes was 1.93 μ mol/L (95% CI 1.38 to 2.47). The expected odds ratio for stroke corresponding to this difference based on previous observational studies was 1.20 (1.10 to 1.31). In our genetic meta- analysis (n=13 928) the odds ratio for stroke was 1.26 (1.14 to 1.40) for TT versus CC homozygotes, similar to the expected odds ratio (p=0.29). Consistency between the odds ratios was preserved in analyses by age- group, ethnic background, and geographical location. Interpretation The observed increase in risk of stroke among individuals homozygous for the MTHFR T allele is close to that predicted from the differencesin homocysteine concentration conferred by this variant. This concordance is consistent with a causal relation between homocysteine concentration and stBackground Individuals homozygous for the T allele of the MTHFR C677T polymorphism have higher plasma homocysteine concentrations (the phenotype) than those with the CC genotype, which, if pathogenetic, should put them at increased risk of stroke. Since this polymorphism is distributed randomly during gamete formation, its association with stroke should not be biased or confounded. We investigated consistency between the expected odds ratio for stroke among TT homozygotes, extrapolated from genotype - phenotype and phenotype- disease studies, and the observed odds ratio from a meta- analysis of genotype- disease association studies. Methods We searched MEDLINE and EMBASE up to June, 2003, for all relevant studies on the association between homocysteine concentration and the MTHFR polymorphism, and until December, 2003, for those on the association between the polymorphism and the risk of stroke. Pooled odds ratios and 95% CI were calculated by random- effects and fixed- effects models. Consistency between expected and observed odds ratios was assessed by interaction test. Findings 111 studies met the selection criteria. Among 15 635 people without cardiovascular disease, the weighted mean difference in homocysteine concentration between TT and CC homozygotes was 1.93 μ mol/L (95% CI 1.38 to 2.47). The expected odds ratio for stroke corresponding to this difference based on previous observational studies was 1.20 (1.10 to 1.31). In our genetic meta- analysis (n=13 928) the odds ratio for stroke was 1.26 (1.14 to 1.40) for TT versus CC homozygotes, similar to the expected odds ratio (p=0.29). Consistency between the odds ratios was preserved in analyses by age- group, ethnic background, and geographical location. Interpretation The observed increase in risk of stroke among individuals homozygous for the MTHFR T allele is close to that predicted from the differencesin homocysteine concentration conferred by this variant. This concordance is consistent with a causal relation between homocysteine concentration and st

关 键 词：孟德尔 随机法 基因多态性 等位基因纯合子 比值比 荟萃分析 心血管疾病 发病风险 随机模型 加权平均 

分 类 号：R743.3[医药卫生—神经病学与精神病学]